Multilevel interrogation of H3.3 reveals a primordial role in transcription regulation.

Histones / genetics Gene Expression Regulation Chromatin / genetics Transcription, Genetic Cell Nucleus / metabolism
Asf1 CAF1 Chromatin Epigenetics Functional proteomics H3.3 HIRA Histone variant NASP RBBP4/7 Tetrahymena

Journal

Epigenetics & chromatin
ISSN: 1756-8935
Titre abrégé: Epigenetics Chromatin
Pays: England
ID NLM: 101471619

Informations de publication

Date de publication:
07 04 2023
Historique:
received: 07 02 2023
accepted: 28 03 2023
medline: 10 4 2023
entrez: 6 4 2023
pubmed: 7 4 2023
Statut: epublish

Résumé

Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts. We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes. Our results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

Sections du résumé

BACKGROUND
Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts.
RESULTS
We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes.
CONCLUSION
Our results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

Identifiants

DOI: 10.1186/s13072-023-00484-9 PMID: 37024975 PMC: PMC10080907
pubmed: 37024975
doi: 10.1186/s13072-023-00484-9
pii: 10.1186/s13072-023-00484-9
pmc: PMC10080907
doi:

Substances chimiques

Histones 0
Chromatin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10

Subventions

Organisme : CIHR
ID : FDN-154338
Pays : Canada
Organisme : CIHR
ID : MOP13347
Pays : Canada

Informations de copyright

© 2023. The Author(s).

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Auteurs

Syed Nabeel-Shah (S)

Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada.

Jyoti Garg (J)

Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
Department of Biology, York University, 4700 Keele St, Toronto, M3J 1P3, Canada.

Kanwal Ashraf (K)

Department of Biology, York University, 4700 Keele St, Toronto, M3J 1P3, Canada.

Renu Jeyapala (R)

Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.

Hyunmin Lee (H)

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Department of Computer Science, University of Toronto, Toronto, M5S 1A8, Canada.

Alexandra Petrova (A)

Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.

James D Burns (JD)

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.

Shuye Pu (S)

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.

Zhaolei Zhang (Z)

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada.
Department of Computer Science, University of Toronto, Toronto, M5S 1A8, Canada.

Jack F Greenblatt (JF)

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada.

Ronald E Pearlman (RE)

Department of Biology, York University, 4700 Keele St, Toronto, M3J 1P3, Canada.

Jean-Philippe Lambert (JP)

Department of Molecular Medicine, Cancer Research Center, Big Data Research Center, Université Laval, Quebec City, QC, Canada.
CHU de Québec Research Center, CHUL, 2705 Laurier Boulevard, Quebec City, QC, Canada.

Jeffrey Fillingham (J)

Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada. jeffrey.fillingham@torontomu.ca.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › Multilevel interrogation of H3.3 reveals a...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Multilevel interrogation of H3.3 reveals a...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Multilevel interrogation of H3.3 reveals a...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › Multilevel interrogation of H3.3 reveals a...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › Multilevel interrogation of H3.3 reveals a...